Abstract This manuscript provides a concise surgical review of cystic diseases of the liver. Attention is paid to diagnosis, pre-surgical evaluation, surgical techniques, including laparoscopy, and post-surgical care of the patient with cystic disease of the liver. Keywords Liver cyst • Liver surgery • Hepatobiliary surgery • Cystic disease of the liver • Cystadenoma Introduction Cystic disease of the liver is a frequent indication for surgical consultation as modern cross-sectional imaging identifi es some form of hepatic cystic disease in as high as 18 % of studies [ 1 ]. A myriad of conditions manifest cystic disease of the liver with an equally broad spectrum of prognoses; however, the overall management of cystic diseases within the liver is straightforward provided one adheres to several guiding principles. Furthermore, the widespread application of laparoscopy and intra-operative ultrasound has signifi cantly improved therapeutic options for patients and surgeons. Surgical Considerations The approach to cystic diseases of the liver begins with recognition of four broad classifi cations based upon etiology. These categories are: congenital, neoplastic, traumatic, and infectious. Congenital cysts are, by far, the most prevalent and arise from a defect in production of bile duct basement membrane resulting in cystic J. F. Renz (*) University of Chicago Medicine , 5841 S. Maryland, Room J517 MC5027 , Chicago , IL 60637 , USA e-mail: [email protected] 56 malformation of intrahepatic bile ducts [ 2 , 3 ]. These include simple cysts and adult polycystic liver disease (APLD) [ 3 ]. Neoplastic cysts may be primary or metastatic. Cystadenoma and cystadenocarcinoma may originate within the liver while cystadenocarcinomas from the ovary and pancreas often metastasize to the liver. Traumatic cysts form secondary to liver injury such as disruption of an intrahepatic bile duct or subcapsular hematoma. Infectious cysts include pyogenic liver abscess , hydatid disease, and amoebic abscesses as well as extra-hepatic cysts secondary to retained gallstones from a previous cholecystectomy [ 2 ]. Formulating a robust working hypothesis as to the origin of the cyst is essential to anticipating the optimal surgical therapy. A second principle in approaching cystic liver disease is meticulous analysis of radiologic imaging. Often, patients presenting for surgical consultation have had diagnostic or potentially therapeutic procedures previously performed. These not only include interventional radiologic procedures such as biopsy, needle aspiration, and sclerotherapy but previous surgical fenestration. Complications such as bleeding or infection from these procedures can signifi cantly alter subsequent imaging and the occurrence of a complication may not have been clinically recognized. In situations where any previous procedure has been performed upon a cyst, every effort should be made to obtain as much possible imaging, particularly crosssectional imaging, that was performed prior to the intervention. If surgery is being entertained, recent cross sectional imaging ( computed tomography or magnetic resonance imaging ) will facilitate accurate cyst classifi cation and symptom correlation while reducing the chance of an unanticipated change in surgical plan during surgery. Cross sectional imaging analysis focuses upon four specifi c areas: number of cysts, cyst content, cyst wall architecture, and cyst location. Cysts may be single or multiple with a homogenous or heterogenous cyst content. The cyst wall architecture may be uniform in thickness or irregular in thickness with projections of the cyst wall into the lumen or septations. Lastly, does the cyst location support the patient’s symptoms? Appreciation of multiple closely approximated cysts, heterogeneous cyst content without prior intervention, or any cyst wall architecture that is not completely uniform are indications for further investigation utilizing intraoperative ultrasound and a surgical approach that requires more than simple fenestration. Correlation of cyst location to the patient’s symptoms is particularly important in the management of congenital cysts. Common presenting symptoms include abdominal pain , epigastric bloating, early satiety, and dyspepsia [ 2 ]. Large size (>6 cm), pericapsular or ventral location, and heterogenous content suggesting previous hemorrhage are typically associated with abdominal pain while epigastric bloating, early satiety, and dyspepsia are associated with predominantly left lobe, dorsally located lesions may be symptomatic at a smaller size. Biliary disease, gastro- esophageal refl ux disease, and other common indications of abdominal pain should be excluded prior to offering surgery for abdominal pain secondary to congenital cysts [ 2 ]. J.F. Renz 57 Congenital Cysts Congenital cysts include simple cysts and APLD. Simple cysts are single or multiply scattered, uniform, thin-walled masses with a homogenous, low-viscosity cyst content. Histologically, the cyst lining is simple cuboidal or columnar epithelium that produces a serous fl uid. Large cysts are more frequent in women with a female to male ratio of 4:1 and are uncommon under the age of 40 years. The average reported size of simple cysts is 3 cm and most are asymptomatic. Simple cysts on occasion may rupture into the abdominal cavity causing transient peritoneal discomfort but hemorrhagic rupture is exceedingly rare [ 2 , 3 ]. Simple cysts are ideally approached laparoscopically. The cyst should be carefully examined utilizing intra-operative ultrasound to confi rm a uniform thin lining with no papillary projections into the cyst lumen or hepatic parenchyma. The cyst wall typically demonstrates sharp sonographic echo demarcation secondary to the luminal fl uid interface and compressed hepatic parenchyma [ 4 ]. Simple cyst fl uid is clear and serous; however, a previous hemorrhage may produce a heterogeneous mix. In either case, the cyst should be aspirated and a generous excisional biopsy obtained for histologic evaluation. If a cystadenoma is excluded, the fenestration may proceed to wide excision of the cyst wall. Intra-operative ultrasound can be intermittently utilized to maximize wall excision without encountering major vascular structures. Argon beam coagulation of the remnant epithelial surface can be employed to destroy remaining biliary epithelia and recruit an infl ammatory response but is not mandatory. When operating for a presumed simple cyst, if a cystadenoma cannot be excluded or the cyst content is overtly bilious, fenestration should be abandoned for hepatic resection . If there is a potential cystadenoma, the resection should include at least a 0.5 cm margin with pathologic confi rmation. In the scenario of overtly bilious cyst fl uid, the resection is indicated to completely remove the cyst lining so as to expose biliary radicle(s) for repair. Percutaneous therapies for the management of simple cysts including aspiration and sclerotherapy are available. Aspiration as a diagnostic maneuver to assess symptom alleviation is potentially valuable but should not be considered defi nitive therapy due to a high recurrence rate [ 5 ]. Notably, aspiration will change the radiologic appearance of the cyst. Sclerotherapy may be applied in patients who are poor surgical candidates but its effi cacy is lower than surgical fenestration [ 6 ]. APLD is most often identifi ed in the presence of polycystic kidney disease and results from a mutation in the PKD-1 or PKD-2 gene. A rare mutant of the protein kinase C gene, 80 K-H, can manifest as isolated APLD. Cysts appear similar to simple cysts except they are far more numerous, generally smaller in size, bilobar in distribution, and are associated with numerous microcysts in their vicinity. A female predominance is observed with pregnancy and hormonal therapy implicated in APLD progression. Renal failure also correlates with APLD progression. APLD is associated with cerebral artery aneurysm, valvular heart disease, inguinal hernia, and diverticulosis [ 2 , 3 ]. 5 Cystic Diseases of the Liver 58 Symptoms may result from infection, traumatic rupture, intracystic hemorrhage, Budd-Chiari syndrome, dyspnea, or extrinsic compression of the biliary or digestive tracts [ 3 ]. Excluding infection, the occurrence of symptoms should be interpreted as the result of excessive abdominal volume and therapeutic options designed to signifi cantly reduce volume rather than attention to an isolated cyst(s). Currently, there are no medical therapies to reduce disease burden or prevent progression [ 2 ]. Surgical therapy designed to substantially reduce abdominal volume offers the greatest promise for durable benefi t. To this end, substantial knowledge in heptobiliary surgery is required to tailor procedures according to symptoms, cyst distribution, parenchymal preservation, biliary and vascular anatomy. Fenestration or dominant cyst wall excision is unlikely to yield long-term benefi t. Instead, surgical resection , preferably laparoscopically, should be optimized to remove the highest concentration of cysts at the initial operation [ 7 ]. This yields the greatest chance of durable relief while preserving hepatic function as subsequent attempts at extensive resections following previous surgical procedures become signifi cantly more diffi cult and risk parenchymal ischemia. For extensive disease, APLD progression mandates consideration of liver transplant ation [ 7 ]. While not a true cystic disease, Caroli’s disease does deserve mention as it may enter the differential diagnosis of a patient presenting with presumed intra-hepatic cysts. Caroli’s disease is an autosomal recessive congenital malformation with a female predominance that results from incomplete gestational biliary duct formation. The biliary dilations are not true cysts as each communicates with the biliary system. Hence, a magnetic resonance cholangiopancreatography will demonstrate segmental dilatations in one or both hepatic lobes that often contain choledocholiths [ 2 ]. The most common presentation of Caroli’s disease is cholangitis secondary to impaired biliary excretion. Caroli’s disease may coexist with congenital hepatic fi brosis and predisposes to cholangiocarcinoma. When unilobar, more commonly the left hepatic lobe, surgical resection to include the extra-hepatic biliary tree with a Roux-en-Y hepaticojejunostomy is preferred. Extensive bilobar disease is a much more diffi cult condition that mandates ursodeoxycholic acid, surveillance imaging for cholangiocarcinoma, judicious instrumentation of the biliary tree when absolutely necessary and potential consideration of liver transplant ation [ 2 ]. Neoplastic Cysts Neoplastic cysts may be primary or metastatic. Primary cystadenocarcinoma of the liver is uncommon as is its precursor lesion a cystadenoma . Together, they comprise <1 % of intra-hepatic cystic lesions observed on cross-sectional imaging [ 2 , 8 ]. Metastatic cystic lesions, most commonly from the pancreas or ovary are equally uncommon; however, both primary and metastatic cystic lesions carry a poor prognosis mandating precise surgical management from the onset to optimize outcome. Essential to properly managing these lesions is maintaining a high index of suspicion. This is best achieved from the very fi rst examination of cross sectional J.F. Renz 59 imaging. As previously stated, every effort should be made to observe imaging that does not refl ect interventions performed upon the cyst. The observation of heterogeneous or mucinous cyst content, septations, papillary projections, irregular wall thickness or the presence of a mass associated with the cyst is not consistent with congenital cystic disease. If any of the above are observed, serologic studies to exclude hydatid should be performed before proceeding to the operating room for excision of a presumed neoplastic cyst. While carbohydrate antigen 19-9 and carcinoembryonic antigen levels may be elevated in neoplastic cystic fl uid, these fi ndings are not diagnostic and attempts to obtain diagnostic cyst fl uid sampling pre-operatively are not encouraged [ 9 ]. Surgical planning for a presumed neoplastic cyst involves formal hepatic resection to obtain an appropriate surgical margin. If a neoplastic cyst is entertained after initiating a fenestration procedure, conversion from a laparoscopic to an open procedure may afford improved source control and limit potential tumor distribution within the abdomen. Whenever one is contemplating reoperation for a recurrent cyst, particularly if the patient derived their initial care from another provider, caution in reviewing the surgical procedure and pathology is prudent as is the performance of a formal hepatic resection . Traumatic Cysts The incidence of traumatic cysts within the liver is increasing secondary to the widespread applicability of percutaneous diagnostic and therapeutic interventions. Traumatic cysts are a misnomer as they are technically pseudocyst cavities created secondary to hepatic injury without an epithelial lining. These cavities can be the result of a subcapsular hematoma, an intra-parenchymal hematoma, or coagulative necrosis following a parenchymal ablative procedure. Clinically, these patients present with constitutional signs of sepsis following bacterial superinfection of the pseudocyst. Initial treatment with broad-spectrum antibiotics and percutaneous drainage is often successful with surgical debridement and drainage ( laparoscopic or open ) reserved for unique circumstances [ 2 , 10 ]. Infectious Cysts Infectious cysts include pyogenic liver abscess , hydatid disease, fungal, and amoebic abscesses as well as extra-hepatic cysts secondary to retained gallstones from a previous cholecystectomy [ 10 ]. Irrespective of the etiologic agent, the approach to infectious cysts uniformly involves diagnosis , systemic treatment, cyst evacuation, and prevention of re-infection. Appropriate history and physical examination, in addition to serologic assay, are central to the early diagnosis of hydatid disease and amebiasis. An infectious etiology should also be appropriately excluded in the 5 Cystic Diseases of the Liver 60 pre-operative evaluation of a neoplastic cyst. Following diagnosis, systemic treatment is initiated prior to evacuation of the cyst. Traditional operative therapy for infectious cysts is rapidly being replaced by percutaneous drainage with surgery reserved for larger cysts (>5 cm in diameter) or percutaneous treatment failures [ 11 ]. Following drainage, treatment is continued to prevent superinfection while the liver remodels. Pyogenic liver abscess (PLA) has historically resulted from portal venous seeding of bacteria from appendicitis or diverticulitis. In immunocompromised patients, Candida should be a consideration; however, improved medical therapy has signifi – cantly lowered the incidence of PLA from these etiologies. Instead, PLA is now the most commonly the result of biliary tract disease or hepatic parenchymal ablation [ 2 ]. Hepatic parenchymal ablation with superinfection has been previously described but biliary tract manipulation, either instrumentation ( ERCP ) or stenting, along with obstruction from a benign or malignant stricture can incite a PLA [ 2 , 10 ]. Attention to the patient’s medical history in approaching a PLA guides therapy. In the setting of a PLA secondary to bacterial/fungal seeding, the routine algorithm advocated above with percutaneous aspiration /drainage is recommended. The decision to leave a drain should be tailored to the situation as repetitive aspiration has been demonstrated to be equivalent to drainage in smaller (<5 cm diameter) PLA [ 12 ]. When a PLA from a biliary source is suspected, the treatment should be surgical, typically a hepatic resection , and directed at the underlying biliary etiology. Hydatid disease is caused by Echinococcus granulosus or Echinococcus multilocularis where humans are an intermediate host. Endemic areas include South America, Middle East, Far East, East Africa, Australia and the Mediterranean countries where sheep are plentiful. The most common presentation is persistent right upper quadrant pain secondary to cyst expansion and hepatic parenchymal compression; however, other serious complications from erosion of hydatid cysts into biliary and vascular structures have been reported. Cross-sectional imaging and an eosinophilia can be highly sensitive in conjunction with an appropriate history but the diagnosis is confi rmed serologically. Surgical management has dramatically changed from traditional open hepatic resection to percutaneous drainage with laparoscopy as indicated according to the above infectious cyst protocol [ 2 , 13 , 14 ]. Amebic hepatic abscess secondary to Entamoeba histolytica should be considered in toxic patients a recent history of visiting tropical climates. The patients classically present with acute abdominal pain and fever. Cross sectional imaging demonstrates a single large loculated abscess with a heterogeneous content. The widespread parenchymal necrosis from the protozoan produces the “anchovy sauce” appearance of the cystic fl uid. Diagnosis is by serology but, unlike hydatid disease, these patients do not exhibit eosinophilia. Treatment is as outlines for infectious cysts utilizing metronidazole, emetine hydrochloride, chloroquine phosphate, or diloxanide furoate. One unique consideration in amebic abscess is their proclivity to rupture. When located near the hepatic capsule, early aspiration and drainage is indicated [ 2 ]. J.F. Renz 61 Summary Cystic diseases of the liver are common and multifactorial in origin. A standardized approach to an hepatic cyst, as outlined above, begins with a meticulous history and physical examination to broadly hypothesize the cyst etiology as congenital, neoplastic, traumatic, or infectious. Detailed radiologic analysis can then be incorporated evaluating the number, location, cyst content, cyst content heterogeneity, and wall characteristics to refi ne the hypothesis. Serologic studies add further data for differentiating complex infectious from neoplastic cysts. 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